Interactions of designer antibiotics and the bacterial ribosomal aminoacyl-tRNA site

James B. Murray, Samy O. Meroueh, Rupert J.M. Russell, Georg Lentzen, Jalal Haddad, Shahriar Mobashery

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

The X-ray crystal structures for the complexes of three designer antibiotics, compounds 1, 2, and 3, bound to two models for the ribosomal aminoacyl-tRNA site (A site) at 2.5-3.0 Å resolution and that of neamine at 2.8 Å resolution are described. Furthermore, the complex of antibiotic 1 bound to the A site in the entire 30S ribosomal subunit of Thermus thermophilus is reported at 3.8 Å resolution. Molecular dynamics simulations revealed that the designer compounds provide additional stability to bases A1492 and A1493 in their extrahelical forms. Snapshots from the simulations were used for free energy calculations, which revealed that van der Waals and hydrophobic effects were the driving forces behind the binding of designer antibiotic 3 when compared to the parental neamine.

Original languageEnglish (US)
Pages (from-to)129-138
Number of pages10
JournalChemistry and Biology
Volume13
Issue number2
DOIs
StatePublished - Feb 1 2006
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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